Dr. Elmets major research interests focus on environmental influences on the skin and on the immune system. His research has investigated how ultraviolet light and other environmental agents interact with immunological function of the skin. Initial studies in mice showed that in vivo exposure of murine skin produced a local deficiency in the antigen presenting function of skin, thereby resulting in the preferential generation of antigen specific regulatory T-cells. Studies examining the mechanism by which ultraviolet radiation impaired the function of antigen presenting cells in in vitro systems showed that ultraviolet radiation inhibited expression of the adhesion molecule CD54 (ICAM-1), which was at least in part, responsible for deficient activation of T-cells. More recent studies have assessed the cutaneous and immunological effects of photodynamic therapy. Those studies were the first to show that photodynamic therapy has immunosuppressive effects which may reduce the overall efficacy of this form of cancer therapy.

Another major research interest is the immunogenicity of topically applied chemical carcinogens. Using polyaromatic hydrocarbons as prototypic carcinogenic chemicals, he has shown that topical application of these compounds results in the development of allergic contact hypersensitivity. Metabolism of the compounds is required for the development of this response which only occurs in mice with certain MHC haplotypes and in Ah receptor positive strains of mice. Bases on these results, he has developed the hypothesis that the presence of allergic contact hypersensitivity to polyaromatic hydrocarbons serves to protect mice from the carcinogenic effects of these agents. In support of this hypothesis, he has shown the MHC congenic strains of mice that do not develop polyaromatic hyrdrocarbon contact hypersensitivity are at increased risk for development of skin cancers by those agents.

A third area of research interest is in chemoprevention of skin cancer. In both animals and humans green tea polyphenols have a protective effect on UV-induced damage to the skin. He has shown in animals that this agent protects against UV induced immunosuppression and in humans it prevents the clinical and histological features of sunburn reaction and DNA damage. He is also investigating whether celecoxib exerts a chemopreventive effect against actinic keratoses in humans and whether topical application of DNA repair enzymes will prevent the development of non-melanoma skin cancers in renal transplant patients.

Ahmad I, Simanyi E, Guroji P, Tamimi IA, Delarosa HJ, Nagar A, Nagar P, Katiyar SK, Elmets CA, Yusuf N. Toll-Like Receptor-4 Deficiency Enhances Repair of Ultraviolet Radiation Induced Cutaneous DNA Damage by Nucleotide Excision Repair Mechanism. J Invest Dermatol. 2013 Dec 10.

Guerrero CE, Elewski BE, Elmets CA. Treatment of nonmelanoma skin cancer. JAMA Intern Med. 2013 Dec 9;173(22):2096-7.

Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Begolka WS, Sidbury R. Guidelines of care for the management of atopic dermatitis: Section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2013 Nov 27. pii: S0190-9622(13)01095-5.

Arumugam A, Weng Z, Talwelkar SS, Chaudhary SC, Kopelovich L, Elmets CA, Afaq F, Athar M. Inhibiting Cycloxygenase and Ornithine Decarboxylase by Diclofenac and Alpha-Difluoromethylornithine Blocks Cutaneous SCCs by Targeting Akt-ERK Axis. PLoS One. 2013 Nov 8;8(11):e80076.

Chaudhary SC, Singh T, Talwelkar SS, Srivastava RK, Arumugam A, Weng Z, Elmets CA, Afaq F, Kopelovich L, Athar M. Erb-041, an estrogen receptor beta agonist inhibits skin photocarcinogenesis in SKH-1 hairless mice by down-regulating WNT signaling pathway. Cancer Prev Res (Phila). 2013 Dec 19.

Ryan C, Korman NJ, Gelfand JM, Lim HW, Elmets CA, Feldman SR, Gottlieb AB, Koo JY, Lebwohl M, Leonardi CL, Van Voorhees AS, Bhushan R, Menter A. Research gaps in psoriasis: Opportunities for future studies. J Am Acad Dermatol. 2014 Jan;70(1):146-67.

Pal HC, Sharma S, Strickland LR, Agarwal J, Athar M, Elmets CA, Afaq F. Delphinidin reduces cell proliferation and induces apoptosis of non-small-cell lung cancer cells by targeting EGFR/VEGFR2 signaling pathways. PLoS One. 2013 Oct 4;8(10):e77270.

Srivastava RK, Li C, Chaudhary SC, Ballestas ME, Elmets CA, Robbins DJ, Matalon S, Deshane JS, Afaq F, Bickers DR, Athar M. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption. Toxicol Appl Pharmacol. 2013 Nov 1;272(3):879-87.

Li C, Srivastava RK, Elmets CA, Afaq F, Athar M. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein. Biochem Biophys Res Commun. 2013 Sep 6;438(4):607-12.

Elmets CA, Athar M. Milestones in photocarcinogenesis. J Invest Dermatol. 2013 Jul 1;133(E1):E13-7

Elmets CA. Introduction to milestones in photobiology. J Invest Dermatol. 2013 Jul 1;133(E1):E1.

Pal HC, Sharma S, Elmets CA, Athar M, Afaq F. Fisetin inhibits growth, induces G₂ /M arrest and apoptosis of human epidermoid carcinoma A431 cells: role of mitochondrial membrane potential disruption and consequent caspases activation. Exp Dermatol. 2013 Jul;22(7):470-5.

Vaid M, Prasad R, Singh T, Elmets CA, Xu H, Katiyar SK. Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells. Biochem
Pharmacol. 2013 Apr 15;85(8):1066-76.

Mishra V, Daniel RC, Elmets CA, Levin A, Elewski BE. Palmoplantar pustulosis with fulminant dystrophic 20-nail psoriasis in a patient receiving adalimumab therapy. J Drugs Dermatol. 2013 Jan;12(1):16-7.

Vaid M, Singh T, Prasad R, Elmets CA, Xu H, Katiyar SK. Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice. Cancer Prev Res (Phila). 2013 Mar;6(3):242-52.

Chaudhary SC, Singh T, Kapur P, Weng Z, Arumugam A, Elmets CA, Kopelovich L, Athar M. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis. Toxicol Appl Pharmacol. 2013 May 1;268(3):249-55.

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 Active  Grant Support

VA Merit Review
Principal Investigator
Project entitled “ Host Defense Mechanisms in Polyaromatic Hydrocarbon Carcinogeneis “
Period: 09/01/2006 - 04/30/2014

National Institutes of Health
Principal Investigator
Skin Disease Research Center
Period: 4/30/04 – 8/31/14